Remotely triggered micro-shock wave responsive drug delivery system for resolving diabetic wound infection and controlling blood sugar levels

A novel, micro-shock wave responsive spermidine and dextran sulfate microparticle was developed. Almost 90% of the drug release was observed when the particles were exposed to micro-shock waves 5 times. Micro-shock waves served two purposes; of releasing the antibiotic from the system and perhaps disrupting the S. aureus biofilm in the skin infection model. A combination of shock waves with ciprofloxacin loaded microparticles could completely cure the S. aureus infection lesion in a diabetic mouse model. As a proof of concept insulin release was triggered using micro-shock waves in diabetic mice to reduce the blood glucose level. Insulin release could be triggered for at least 3 days by exposing subcutaneously injected insulin loaded particles.

Controlled Release of Salicylic Acid from Biodegradable Cross-Linked Polyesters

The purpose of this work was to develop a family of crosslinked poly(xylitol adipate salicylate)s with a wide range of tunable release properties for delivering pharmacologically active salicylic acid. The synthesis parameters and release conditions were varied to modulate polyester properties and to understand the mechanism of release. Varying release rates were obtained upon longer curing (35% in the noncured polymer to 10% in the cured polymer in 7 days). Differential salicylic acid loading led to the synthesis of polymers with variable cross-linking and the release could be tuned (100% release for the lowest loading to 30% in the highest loading). Controlled release was monitored by changing various factors, and the release profiles were dependent on the stoichiometric composition, pH, curing time, and presence of enzyme. The polymer released a combination of salicylic acid and disalicylic acid, and the released products were found to be nontoxic. Minimal hemolysis and platelet activation indicated good blood compatibility. These polymers qualify as ``bioactive'' and ``resorbable'' and can, therefore, find applications as immunomodulatory resorbable biomaterials with tunable release properties.

Quantitative metabolic profiling of NMR spectral signatures of branched chain amino acids in blood serum

Branched Chain Amino Acids (BCAAs) are related to different aspects of diseases like pathogenesis, diagnosis and even prognosis. While in some diseases, levels of all the BCAAs are perturbed; in some cases, perturbation occurs in one or two while the rest remain unaltered. In case of ischemic heart disease, there is an enhanced level of plasma leucine and isoleucine but valine level remains unaltered. In `Hypervalinemia', valine is elevated in serum and urine, but not leucine and isoleucine. Therefore, identification of these metabolites and profiling of individual BCAA in a quantitative manner in body-fluid like blood plasma/serum have long been in demand. H-1 NMR resonances of the BCAAs overlap with each other which complicates quantification of individual BCAAs. Further, the situation is limited by the overlap of broad resonances of lipoprotein with the resonances of BCAAs. The widely used commercially available kits cannot differentially estimate the BCAAs. Here, we have achieved proper identification and characterization of these BCAAs in serum in a quantitative manner employing a Nuclear Magnetic Resonance-based technique namely T-2-edited Correlation Spectroscopy (COSY). This approach can easily be extended to other body fluids like bile, follicular fluids, saliva, etc.

Efficient and practical synthesis of modular chiral beta-organochalcogeno amines, ArYCH2CH(R)NH2, and single crystal structures of (S) - MsOCH2CH(Bz)NH3+ center dot Cl- and (R)-MsOCH2CH(Ph)NH3+ center dot Cl-

Modular chiral I3-organochalcogeno amines, ArYCH2CH(R)NH2 (4a-4g) where R = Me, Bz, Ph; and ArY = PhS, BzSe and 4-MeOC6H4Te respectively have been synthesized and characterized. Compounds 4a-4g were synthesized (Method II) from chiral aminoalkyl 13-methanesulfonate hydrochlorides, MsOCH2CH(R)NH3+ center dot Cl- (2a-2c) through nucleophilic displacement of MsO- with organochalcogenolate (ArY-). In another attempt (Method I) chiral beta-organotelluro amines (4a-4c) were prepared by deprotection of chiral N-boc I3-organotelluro amides, 4-MeOC6H4TeCH2CH(R)NH-Boc (3a-3c), which in turn, 13,-,1 were made from chiral N-boc 13-methanesulfonate amides (la-lc) and ArTeNa. 1H, and FTIR spectra of all the compounds (3a-3c and 4a-4g) were characteristic. The composition of 3a-3c was determined by elemental analysis. The a]TD values of 3b-3c and 4a-4g were determined. The single crystal structures of (S)-2b and (R)-2c were determined by X-Ray diffraction studies. Both (S)-2b and (R)2c were crystallized in orthorhombic system and the Flack parameter x was found 0.08(12) and 0.00(2) respectively. The crystal of (S)-2b contain two asymmetric units with gauche (A) and staggered (B) conformations. There are NH Cl-, NH-O and CH-O intra and intermolecular secondary interactions in (S)-2b and (R)-2c resulting in supramolecular structures. (C) 2015 Elsevier By. All rights reserved.

Mycobacterium tuberculosis WhiB3 Responds to Vacuolar pH-induced Changes in Mycothiol Redox Potential to Modulate Phagosomal Maturation and Virulence.

The ability of Mycobacterium tuberculosis to resist intraphagosomal stresses, such as oxygen radicals and low pH, is critical for its persistence. Here, we show that a cytoplasmic redox sensor, WhiB3, and the major M. tuberculosis thiol, mycothiol (MSH), are required to resist acidic stress during infection. WhiB3 regulates the expression of genes involved in lipid anabolism, secretion, and redox metabolism, in response to acidic pH. Furthermore, inactivation of the MSH pathway subverted the expression of whiB3 along with other pH-specific genes in M. tuberculosis. Using a genetic biosensor of mycothiol redox potential (E-MSH), we demonstrated that a modest decrease in phagosomal pH is sufficient to generate redox heterogeneity in E-MSH of the M. tuberculosis population in a WhiB3-dependent manner. Data indicate that M. tuberculosis needs low pH as a signal to alter cytoplasmic E-MSH, which activates WhiB3-mediated gene expression and acid resistance. Importantly, WhiB3 regulates intraphagosomal pH by down-regulating the expression of innate immune genes and blocking phagosomal maturation. We show that this block in phagosomal maturation is in part due to WhiB3-dependent production of polyketide lipids. Consistent with these observations, Mtb Delta whiB3 displayed intramacrophage survival defect, which can be rescued by pharmacological inhibition of phagosomal acidification. Last, Mtb Delta whiB3 displayed marked attenuation in the lungs of guinea pigs. Altogether, our study revealed an intimate link between vacuolar acidification, redox physiology, and virulence in M. tuberculosis and discovered WhiB3 as crucial mediator of phagosomal maturation arrest and acid resistance in M. tuberculosis.

Studies on Carbon Mediated Paste Screen Printed Sensors for Blood Glucose Sensing Application

Ready-to-use screen printed glucose sensors are fabricated using Prussian Blue (PB) and Cobalt Phthalocyanine (CoPC) mediated carbon inks as working electrodes. The reference and counter electrodes are screen printed using silver/silver chloride and graphitic carbon paste respectively. The screen printed reference electrodes (internal reference electrode (IRE)) are found to be stable for more than 60 minutes when examined with saturated calomel electrode. Optimal operating voltage for PB and CoPC screen printed sensors are determined by hydrodynamic voltammetric technique. Glucose oxidase is immobilized on the working electrodes by cross-linking method. PB mediated glucose sensor exhibits a sensitivity of 5.60 mA cm(-2)/mM for the range, 10 to 1000 mu M. Sensitivity of CoPC mediated glucose sensor is found to be 5.224 mu A cm(-2)/mM and amperometeric response is linear for the range, 100 to 1500 mu M. Interference studies on the fabricated glucose sensors are conducted with species like uric acid and ascorbic acid. PB mediated sensors showed a completely interference-free behavior. The sensing characteristics of PB mediated glucose sensors are also studied in diluted human serum samples and the results are compared with the values obtained through standard clinical method. The co-efficient of variation is found to be less than 5%. (C) 2015 The Electrochemical Society. All rights reserved.

Integration of holographic sensors into microfluidics for the real-time pH sensing of L. casei metabolism

We describe developments in the integration of analyte specific holographic sensors into PDMS-based microfluidic devices for the purpose of continuous, low-impact monitoring of extra-cellular change in micro-bioreactors. Holographic sensors respond to analyte concentration via volume change, which makes their reduction in size and integration into spatially confined fluidics difficult. Through design and process modification many of these constraints have been addressed, and a microfluidics-based device capable of real-time monitoring of the pH change caused by Lactobacillus casei fermentation is presented as a general proof-of-concept for a wide array of possible devices.

Calidad bromatológica, organolépticas y ph en ensilaje de pasto cubano (Pennisetum purpureum x Pennisetumtyphoides) CV. CT-115 bajo el efecto de cuatro aditivos utilizados en la conservación de forraje en la finca Santa Rosa, Sabana Grande, Managua

Este estudio se realizó en la finca Santa Rosa propiedad de la Universidad Nacional Agraria en Managua, con el objetivo de evaluar lascaracterísticas organolépticas (olor, color, textura), temperatura, pH y calidadbromatológica (materia seca MS, proteína bruta PB y fibra neutro detergente FND), en ensilaje de pasto Pennisetum purpureum x PennisetumtyphoidesCV. CT- 115, bajo el efecto de cuatro aditivos para conservación: melaza, fermento de malanga, fermento de yuca y fermento de papa. El pasto fue cosechado a 60 días con tamaño de picado de2.5 cm, aplicando 800g de melaza comercial y 150cc de aditivo en cada bolsa de ensilaje, la apertura de las silobolsas se realizó a 20 días, seguidamente fueron evaluados porun jurado de expertos (4 personas). El Diseño utilizado fue un DCA con cuatro tratamientos: T1 ensilaje (CT- 115+melaza), T2 ensilaje (CT-115+melaza+fermento de malanga), el T3 ensilaje (CT- 115+melaza+fermento de yuca) y T4 ensilaje (CT-115+melaza+fermento de papa) y cuatro repeticiones, para 16 unidades experimentales. Los resultados para la variable olor en aproximación al valor ideal fueron del 87.55% para T1; T2: 88.55%, T3: 72.33% y T4: 77.74%; con respecto al color el T1 alcanzó el valor: 77.08%, T2: 100%, T3: 89.58% y T4: 85.41%; en cuanto a la textura los resultados fueron para T1, T2, y T3 del 100%, para T4: 93.77%.La variable temperatura reportó resultadosde 31.75°C para T1, T2 y T3: 32.00°C y T4: 31.50°C.Para la variable pH se encontró que el T2 presentó diferencias significativas (p<0.05) con respecto al T1 y T4, al mismo tiempo presentó diferencias altamente significativas (p<0.01) con el T3. El T1 y T4 no presentaron diferencias significativas, pero presentaron diferencias significativas (p<0.05) con respecto al T3, y obtuvieron medias (por Tukey) para T1 de 4.66, T2: 4.87, T3: 4.22 y T4: 4.45.Los resultados de calidad bromatológica para MS por tratamiento fueron29.94%, 27.84%, 28.20% y 32.59%, respetivamente. La PB alcanzó valores de 5.22%, 4.64%, 4.75% y 4.76%, por tratamiento respectivamente. La FND presentó valores por tratamiento de 55.41%, 64.10%, 63.06% y 57.01%, respectivamente. Con base en estos resultados se estima que el ensilaje del T2 presentó los mejores resultados en cuanto a características organolépticas, aunque bromatológicamente no supero al testigo (T1), el uso de aditivos de fermentos en el ensilaje mejora su calidad organoléptica.

Determinación de la concentración de pH en hojas de cultivares clonales Spondias purpurea L, en el arboretum Alain Meyrat de la Universidad Nacional Agraria, Managua, Nicaragua

La presente investigación tiene como objetivo determinar la concentración de pH en las hojas de 17 cultivares clónales de Spondias purpurea L, ubicado en el Arboretum Alain Meyrat de la Universidad Nacional Agraria, la metodología utilizada consistió en la recolección del material vegetativo de las cuales se seleccionaron 20 hojas de cada cultivar clonal en buen estado (sanas, verdes y completas). Se procedió medir con ayuda de una balanza el peso verde de las hojas separando los foliolos y el raquis la cuales se rotularon con el nombre de cada cultivar clonal. Para determinar la concentración pH de cada cultivar se recortó los foliolos y el raquis utilizando 3 g de cada muestra, se macera con un mortero hasta obtener materia molida. Una vez macerado los 3 g de cada muestra se determina la solubilidad de las hojas, haciendo uso de solventes como el agua (H₂0), benceno (C₆H₆), etanol (CH₃-CH₂-0H), y tetracloruro de carbono (CCL₄), para ello se utilizó 3 ml de cada solvente. Se empleó el uso de un pHmetro para determinar la concentración de pH de las muestras combinadas con los solventes y pH de la muestra sin solvente. Se obtuvo que el pH del cultivar San franciscano posee mayor contenido de acidez empleando los solventes químicos y el raquis seco para elaborar infusiones, por el contrario las infusiones con los foliolos secos del cultivar Cocer se obtuvo la mayor concentración de acidez

Effects of pH on Growth of Salvinia molesta Mitchell

Growth of giant salvinia ( Salvinia molesta Mitchell) under different pH regimes was examined at the Lewisville Aquatic Ecosystem Research Facility (LAERF) in Lewisville, Texas.(PDF has 5 pages.)

Influence of nutrient intake on antioxidant capacity, muscle damage and white blood cell count in female soccer players

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The Influence of Formulation, Buffering, pH and Divalent Cations on the Activity of Endothall on Hydrilla.

Endothall has been used as an aquatic herbicide for more than 40 years and provides very effective weed control of many weeds. Early research regarding the mechanism-of-action of endothall contradicts the symptomology normally associated with the product. Recent studies suggest endothall is a respiratory toxin but the mechanism-of-action remains unknown. To further elucidate the activity of endothall, several endothall formulations were evaluated for their effects on ion leakage, oxygen consumption and photosynthetic oxygen evolution from hydrilla shoot tips. The influence of pH, buffering and divalent cations was also evaluated. (PDF contains 6 pages.)

High-Throughput Sequencing of microRNAs in Peripheral Blood Mononuclear Cells: Identification of Potential Weight Loss Biomarkers

INTRODUCTION: MicroRNAs (miRNAs) are being increasingly studied in relation to energy metabolism and body composition homeostasis. Indeed, the quantitative analysis of miRNAs expression in different adiposity conditions may contribute to understand the intimate mechanisms participating in body weight control and to find new biomarkers with diagnostic or prognostic value in obesity management. OBJECTIVE: The aim of this study was the search for miRNAs in blood cells whose expression could be used as prognostic biomarkers of weight loss. METHODS: Ten Caucasian obese women were selected among the participants in a weight-loss trial that consisted in following an energy-restricted treatment. Weight loss was considered unsuccessful when <5% of initial body weight (non-responders) and successful when >5% (responders). At baseline, total miRNA isolated from peripheral blood mononuclear cells (PBMC) was sequenced with SOLiD v4. The miRNA sequencing data were validated by RT-PCR. RESULTS: Differential baseline expression of several miRNAs was found between responders and non-responders. Two miRNAs were up-regulated in the non-responder group (mir-935 and mir-4772) and three others were down-regulated (mir-223, mir-224 and mir-376b). Both mir-935 and mir-4772 showed relevant associations with the magnitude of weight loss, although the expression of other transcripts (mir-874, mir-199b, mir-766, mir-589 and mir-148b) also correlated with weight loss. CONCLUSIONS: This research addresses the use of high-throughput sequencing technologies in the search for miRNA expression biomarkers in obesity, by determining the miRNA transcriptome of PBMC. Basal expression of different miRNAs, particularly mir-935 and mir-4772, could be prognostic biomarkers and may forecast the response to a hypocaloric diet.